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EMBRYONIC STEM CELLS |
Department of Microbiology/Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana, USA; Walther Cancer Institute, Indianapolis, Indiana, USA
Key Words. Embryonic stem cells • Survival • Apoptosis • Cytokines/chemokines • Hematopoietic progenitors
Correspondence: Hal E. Broxmeyer, Ph.D., Walther Oncology Center, Indiana University School of Medicine, 950 West Walnut Street, R2-302, Indianapolis, Indiana 46202, USA. Telephone: 317-274-7510; Fax: 317-274-7592; e-mail: hbroxmey{at}iupui.edu
Received September 19, 2005;
accepted for publication November 16, 2005.
Stromal cell–derived factor (SDF)-1/CXCL12, released by murine embryonic stem (ES) cells, enhances survival, chemotaxis, and hematopoietic differentiation of murine ES cells. Conditioned medium (CM) from murine ES cells growing in the presence of leukemia inhibitory factor (LIF) was generated while the ES cells were in an undifferentiated Oct-4 expressing state. ES cell–CM enhanced survival of normal murine bone marrow myeloid progenitors (CFU-GM) subjected to delayed growth factor addition in vitro and decreased apoptosis of murine bone marrow c-kit+lin– cells. ES CM contained interleukin (IL)-1
, IL-10, IL-11, macrophage-colony stimulating factor (CSF), oncostatin M, stem cell factor, vascular endothelial growth factor, as well as a number of chemokines and other proteins, some of which are known to enhance survival/anti-apoptosis of progenitors. Irradiation of ES cells enhanced release of some proteins and decreased release of others. IL-6, FGF-9, and TNF-, not detected prior to irradiation was found after ES cells were irradiated. ES cell CM also stimulated CFU-GM colony formation. Thus, undifferentiated murine ES cells growing in the presence of LIF produce/release a number of biologically active interleukins, CSFs, chemokines, and other growth modulatory proteins, results which may be of physiological and/or practical significance.
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